Radiation therapy is a common modality in the treatment of various malignancies. An untoward side effect of radiation therapy in the treatment of cancer or other disease states is the development of secondary cancers in the treatment area.
Captopril (Capoten, Bristol-Meyers Squibb, Princeton, N.J.) is an inhibitor of angiotensin converting enzyme. Clinically, Captopril has been used extensively in the management of systemic hypertension and congestive heart failure. Captopril was the first orally active inhibitor of angiotensin converting enzyme and is the subject matter of U.S. Pat. No. 4,046,889, issued Sept. 6, 1977 and assigned to Squibb Corporation.
Captopril has been found to have other biologically significant actions in addition to the ability of the drug to inhibit angiotensin converting enzyme. Presumably as a result of the sulphydryl group in its molecular structure, Captopril is a free radical scavenger (Chopra et al, Br. J. Clin. Pharmacol. 27 396-399 1989). Chopra et al suggested that this action may be relevant to the efficacy of the drug in heart failure and other vascular diseases (Chopra et al Br. J. Clin. Pharmacol. 27 396-399, 1989). Captopril has also been found to have antioxidant activity (Roberts and Robinson, Br. J. Rheumatol. 24 128-136 1985). This study was related to the identification of antirheumatic activity of the drug.
Captopril also may inhibit protease activity Kennedy et al. (in Anticarcinogenesis and Radiation Protection, ed. by P. A. Cerutti et al. Plenum Press, N.Y., 1987) reported on investigations of anticarcinogenic actions of various protease inhibitors. Proteases have been postulated to have various roles in cancer cells, and several protease inhibitors were found to be anticarcinogenic.
Besides the use of Captopril clinically in the management of systemic hypertension and congestive heart failure, (Franciosa, J. A. 1987 Angiotensin Coverting Enzyme Inhibitors ed. J. B. Kostis et al. Liss, N.Y., pp. 123-148; Gavras et al supra, pages 93-122), Captopril has been found to Hopewell, Br. J. Cancer, 53 (Suppl VII), 265-267, 1986), and to spare radiation induced pulmonary endothelial dysfunction in rats by the present inventors (Ward and Hinz, Prostaglandin and Lipid Metabolism in Radiation Injury, ed. by T. L. Walden et al, Plenum Press, N.Y., p. 147-158, 1987; Ward et al, Int. J. Radiat. Oncol. Biol. Phys, 15, 135-140, 1988). The results of further investigations of other angiotensin converting enzyme inhibitors as modifiers of pulmonary endothelial dysfunction and fibrosis caused by radiation have been published by the inventors (Ward et al, Radiat. Res. 117,342-350, 1989; Ward et al, Br. J. Radiol. 62,348-354 1989).
Although the aforementioned prior art discloses the use of Captopril in the management of systemic hypertension, congestive heart failure, pulmonary hypertension, diabetic renovascular disease, and rheumatoid arthritis, and the prior art further suggests various mechanisms of action of the drug, no prior art discloses or suggests the use of Captopril or like drugs as an anticarcinogenic agent.
Applicants have found that Captopril can be used in a method of reducing benign and malignant reactions, caused by x-ray or gamma radiation.